Metals can produce varied effects on biochemical processes and it now appears that induction of (metal binding) proteins should be included among the diversity of responses multivalent metal ions elicit in biochemical systems. The induction of a great many proteins (enzymes) has been studied, yet the mechanisms by which this phenomenon is produced in mammalian systems remain obscure. The proposed study is designed to further ellucidate the induction process initiated by cadmium, copper, mercury and zinc (known to bind to metallothionein) and to characterize the proteins induced in response to high levels of the respective metals. Mice will be challenged with chloride salts of copper, cadmium, mercury and zinc in drinking water; at specific time intervals following ingestion of metals, tissues will be excised and analyzed by centrifugation, gel filtration, electrophoresis, liquid scintillation, and immunological techniques. Highly purified metal binding proteins will be characterized by spectrophotometry, amino acid composition, molecular weight analysis, metal analysis, electrophoretic properties and other parameters. In addition, the mechanism of induction will be explored by analysis of chromosomal materials. Hopefully, the study should give insight into molecular events which determine biological tolerance as opposed to toxicity, and should contribute to our understanding of the regulation of specific gene expression.